6-89199838-A-C

Variant names:

• chr6-89199838-A-C
• rs3777530
• NM_002042.5:c.281-409T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002042.5(GABRR1):​c.281-409T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,150 control chromosomes in the GnomAD database, including 48,495 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (48495 hom., cov: 32)
• Consequence: GABRR1 NM_002042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405
• Publications: 4 publications found

Genes affected

GABRR1 (HGNC:4090): (gamma-aminobutyric acid type A receptor subunit rho1) GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. GABRR1 is a member of the rho subunit family. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002042.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR1	NM_002042.5	MANE Select	c.281-409T>G		intron	N/A	NP_002033.2
	GABRR1	NM_001256703.1		c.230-409T>G		intron	N/A	NP_001243632.1
	GABRR1	NM_001256704.1		c.20-409T>G		intron	N/A	NP_001243633.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRR1	ENST00000454853.7	TSL:1 MANE Select	c.281-409T>G		intron	N/A	ENSP00000412673.2
	GABRR1	ENST00000435811.5	TSL:2	c.230-409T>G		intron	N/A	ENSP00000394687.1
	GABRR1	ENST00000369451.7	TSL:5	c.20-409T>G		intron	N/A	ENSP00000358463.3

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120669 AN: 152034 Hom.: 48462 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.800

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.794 AC: 120758 AN: 152150 Hom.: 48495 Cov.: 32 AF XY: 0.799 AC XY: 59400 AN XY: 74380

African (AFR) AF: 0.665 AC: 27574 AN: 41470

American (AMR) AF: 0.837 AC: 12803 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2844 AN: 3468

East Asian (EAS) AF: 0.958 AC: 4966 AN: 5184

South Asian (SAS) AF: 0.768 AC: 3697 AN: 4816

European-Finnish (FIN) AF: 0.912 AC: 9663 AN: 10600

Middle Eastern (MID) AF: 0.815 AC: 238 AN: 292

European-Non Finnish (NFE) AF: 0.831 AC: 56539 AN: 68010

Other (OTH) AF: 0.803 AC: 1696 AN: 2112

Alfa AF: 0.816 Hom.: 31775

Bravo AF: 0.786

Asia WGS AF: 0.838 AC: 2914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.64
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3777530; hg19: chr6-89909557;